a first time in human (ftih) study of gsk3745417 administered to participants with advanced solid tumors

Conditions: Neoplasms

Summary: this study aims to evaluate the safety, tolerability, and preliminary clinical activity and establish a recommended dose of gsk3745417 administered alone (part 1a) or co-administered (part 2a) with dostarlimab in participants with refractory/relapsed solid tumors. both parts will consist of a dose escalation phase.


Eligibility criteria:
inclusion criteria: * participant must be more than or equal to (\>=)18 years of age. * participants with advanced/recurrent solid tumors, who have progressed on, be intolerant of, or ineligible for, all available therapies for which clinical benefit has been established. * histological or cytological documentation of an advanced solid tumor. * participants must provide a fresh biopsy. * measurable disease per response evaluation criteria in solid tumors (recist) version 1.1. * eastern cooperative oncology group (ecog) performance status (ps) 0-1. * adequate organ function per protocol specifications. * male or female participants. * female participants are eligible to participate if they are not breastfeeding or pregnant (or intend to breastfeed or become pregnant). women of childbearing potential must use a highly effective method of contraception. * capable of giving signed informed consent. exclusion criteria: * active autoimmune disease that has required systemic disease modifying or immunosuppressive treatment within the last 2 years. * concurrent medical condition requiring the use of systemic immunosuppressive treatment within 28 days before the first dose of study treatment. * current unstable liver or biliary disease. * history of vasculitis at any time prior to study treatment. * evidence or history of significant active bleeding or coagulation disorder. * active infection requiring systemic treatment, known human immunodeficiency virus infection, or positive test for hepatitis b surface antigen or hepatitis c. * qt duration corrected for heart rate by fridericia's formula (qtcf) more than (\>)450 milliseconds (msec) or qtcf \>480 msec for participants with bundle branch block. * recent history (within the past 6 months) of acute diverticulitis, inflammatory bowel disease, intra-abdominal abscess, or gastrointestinal obstruction. * recent history of allergen desensitization therapy within 4 weeks of starting study treatment. * history or evidence of cardiovascular (cv) risk * recent (within the past 6 months) history of symptomatic pericarditis. * history of idiopathic pulmonary fibrosis, interstitial lung disease, or organizing pneumonia, or evidence of active, non-infectious pneumonitis. * history of (non-infectious) pneumonitis that required steroids or current pneumonitis. * recent history (within 6 months) of uncontrolled symptomatic ascites or pleural effusions. * prior treatment with the following agents: 1. stimulator of interferon genes (sting) agonist at any time. 2. anticancer therapy or investigational therapy or used an investigational device within 28 days or 5 half-lives of the drug, whichever is shorter. 3. checkpoint inhibitors, including programmed death receptor-1 (pd-1), programmed death ligand-1 (pd-l1), pd-l2 and cytotoxic t-lymphocyte-associated antigen 4 (ctla-4) inhibitors within 28 days. 4. prior radiation therapy: permissible if at least 1 non-irradiated measurable lesion is available for assessment according to recist version 1.1 or if a solitary measurable lesion was irradiated, objective progression is documented. * pregnant and/or breast feeding participants or those who plan to become pregnant and/or breastfeed. * receipt of any live vaccine within 30 days of the start of study treatment. * prior allogeneic or autologous bone marrow transplantation or other solid organ transplantation. * major surgery less than or equal to (\<=)28 days before the first dose of study treatment. participants must have also fully recovered from any surgery (major or minor) and/or its complications before initiating study treatment. * participants with signs/symptoms suggestive of coronavirus disease-2019 (covid-19) within 14 days of study entry, or with known exposure to covid-19 within 14 days prior to study entry. * participants are excluded from part 2a of the study if they have known hypersensitivity to dostarlimab or associated excipients.

Keywords: gsk3745417 dostarlimab anti-programmed death receptor-1 (pd-1) monoclonal antibody solid tumor first time in human stimulator of interferon genes sting